A thermodynamic model for acid secretion in frog gastric mucosa has been developed which can account for the coupling between H ion and Cl ion secretion within the framework of electrogenic movement for both ions. This model predicts: a) that Cl ion movement from cell to secreted fluid may be passive, since the electrochemical activity for Cl ion is above equilibrium at both surfaces; b) that the site of active Cl ion transport is the Cl ion/HCO3 ion exchange carrier on the serosal membrane, driven by HCO3 ion exit from the cell; and c) that the free energy necessary to transport H ion from cell to secreted fluid is higher than previously assumed, and may be too high to be supplied by ATP hydrolysis at a reasonable ATP/ADP-Pi ratio. To test this model, microelectrode studies of cytoplasmic electrical potential and chloride activity are proposed, using a serosal route of access to the oxyntic cells which may alleviate some of the previous problems. The use of hyperosmotic conditions and passage of electrical current to determine the free energy at equilibrium for H ion transport will be combined with these studies, and the resulting free energy requirement will be compared with that calculated from measurement of cytoplasmic ATP, ADP, and Pi, to see whether ATP can be the driving force for the H ion pump. These and other similar experiments will also be performed with the gastric mucosa of dogfish, which secretes a more concentrated fluid and thus should provide an even more striking example of these principles. If this model proves correct, it will unite the data previously leading to two fundamentally-different views of the nature of the H ion pump in gastric mucosa of these and other species.